Targeting Type IV Secretion System Proteins to Combat Multidrug-Resistant Gram-positive Pathogens

Laverde, Diana; Probst, Ines; Romero-Saavedra, Felipe; Kropec, Andrea; Wobser, Dominique; Keller, Walter; Grohmann, Elisabeth; Hüebner, Johannes

doi:10.1093/infdis/jix227

Cited by 13 publications

(12 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Currently, the best characterized T4SSs from Gram + bacteria are those encoded by the Enterococcus faecalis sex-pheromone responsive plasmid pCF10 (Li et al ., 2012; Clewell et al ., 2014; Laverde Gomez et al . ; 2014; Bhatty et al ., 2015; Whitaker et al ., 2015; Bhatty et al ., 2017), C. perfringens plasmid pCW3 (Bantwal et al ., 2012; Porter et al , 2012; Wisniewski et al ., 2015; 2016; Wisniewski and Rood, 2017) and broad-host-range plasmid pIP501 originally isolated from S. agalactiae (Arends et al ., 2013; Goessweiner-Mohr et al, 2013a and b; 2014a and b; Fercher et al ., 2016; Grohmann et al , 2016; Kohler et al ., 2017; Laverde et al ., 2017). The conjugation machines in Gram + species differ from their Gram − species counterparts mainly by lacking the outer membrane core complex and the VirB11 ATPase.…”

Section: Conjugative Transfer Systemsmentioning

confidence: 99%

Type IV secretion in Gram‐negative and Gram‐positive bacteria

Grohmann

Christie

Waksman

et al. 2018

Molecular Microbiology

Self Cite

289

285

View full text Add to dashboard Cite

Summary Type IV secretion systems (T4SSs) are versatile multiprotein nanomachines spanning the entire cell envelope in Gram‐negative and Gram‐positive bacteria. They play important roles through the contact‐dependent secretion of effector molecules into eukaryotic hosts and conjugative transfer of mobile DNA elements as well as contact‐independent exchange of DNA with the extracellular milieu. In the last few years, many details on the molecular mechanisms of T4SSs have been elucidated. Exciting structures of T4SS complexes from Escherichia coli plasmids R388 and pKM101, Helicobacter pylori and Legionella pneumophila have been solved. The structure of the F‐pilus was also reported and surprisingly revealed a filament composed of pilin subunits in 1:1 stoichiometry with phospholipid molecules. Many new T4SSs have been identified and characterized, underscoring the structural and functional diversity of this secretion superfamily. Complex regulatory circuits also have been shown to control T4SS machine production in response to host cell physiological status or a quorum of bacterial recipient cells in the vicinity. Here, we summarize recent advances in our knowledge of ‘paradigmatic’ and emerging systems, and further explore how new basic insights are aiding in the design of strategies aimed at suppressing T4SS functions in bacterial infections and spread of antimicrobial resistances.

show abstract

Section: Conjugative Transfer Systemsmentioning

confidence: 99%

Type IV secretion in Gram‐negative and Gram‐positive bacteria

Grohmann

Christie

Waksman

et al. 2018

Molecular Microbiology

Self Cite

289

285

View full text Add to dashboard Cite

show abstract

“…Antibiotic resistance transfer of selected ISS-isolates was studied in biparental matings (Laverde et al, 2017). Isolates resistant to tetracycline, gentamicin or erythromycin and harboring a plasmid >20 kbp were selected as donors, plasmid-free S. aureus 04-02981 and E. faecalis OG1X were used as recipients.…”

Section: Resultsmentioning

confidence: 99%

Biofilm Forming Antibiotic Resistant Gram-Positive Pathogens Isolated From Surfaces on the International Space Station

et al. 2019

Self Cite

View full text Add to dashboard Cite

The International Space Station (ISS) is a closed habitat in a uniquely extreme and hostile environment. Due to these special conditions, the human microflora can undergo unusual changes and may represent health risks for the crew. To address this problem, we investigated the antimicrobial activity of AGXX®, a novel surface coating consisting of micro-galvanic elements of silver and ruthenium along with examining the activity of a conventional silver coating. The antimicrobial materials were exposed on the ISS for 6, 12, and 19 months each at a place frequently visited by the crew. Bacteria that survived on the antimicrobial coatings [AGXX® and silver (Ag)] or the uncoated stainless steel carrier (V2A, control material) were recovered, phylogenetically affiliated and characterized in terms of antibiotic resistance (phenotype and genotype), plasmid content, biofilm formation capacity and antibiotic resistance transferability. On all three materials, surviving bacteria were dominated by Gram-positive bacteria and among those by Staphylococcus, Bacillus and Enterococcus spp. The novel antimicrobial surface coating proved to be highly effective. The conventional Ag coating showed only little antimicrobial activity. Microbial diversity increased with increasing exposure time on all three materials. The number of recovered bacteria decreased significantly from V2A to V2A-Ag to AGXX®. After 6 months exposure on the ISS no bacteria were recovered from AGXX®, after 12 months nine and after 19 months three isolates were obtained. Most Gram-positive pathogenic isolates were multidrug resistant (resistant to more than three antibiotics). Sulfamethoxazole, erythromycin and ampicillin resistance were most prevalent. An Enterococcus faecalis strain recovered from V2A steel after 12 months exposure exhibited the highest number of resistances (n = 9). The most prevalent resistance genes were ermC (erythromycin resistance) and tetK (tetracycline resistance). Average transfer frequency of erythromycin, tetracycline and gentamicin resistance from selected ISS isolates was 10−5 transconjugants/recipient. Most importantly, no serious human pathogens such as methicillin resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococci (VRE) were found on any surface. Thus, the infection risk for the crew is low, especially when antimicrobial surfaces such as AGXX® are applied to surfaces prone to microbial contamination.

show abstract

“…for the inhibition of TraM, the VirB8-homolog associated with the pIP501-encoded T4SS as well as other Gram + conjugation machines. Anti-TraM antibodies directed against the VirB8-homolog from plasmid pIP501 considerably reduced the survival of clinical E. faecalis and S. aureus strains harboring a putative T4SS in vitro and in an in vivo mouse infection model (Laverde et al, 2017). A recent study also established the value of testing the efficacy of small molecule inhibitors shown to block the production of phylogenetically unrelated pilus assembly or secretion systems for effects on T4SS biogenesis or function.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, the best characterized T4SSs from Gram + bacteria are those encoded by the Enterococcus faecalis sex-pheromone responsive plasmid pCF10 (Li et al, 2012;Clewell et al, 2014;Laverde Gomez et al;Bhatty et al, 2015;Whitaker et al, 2015;Bhatty et al, 2017), C. perfringens plasmid pCW3 (Bantwal et al, 2012;Porter et al, 2012;Wisniewski et al, 2015;2016; Rood, 2017) and broad-host-range plasmid pIP501 originally isolated from S. agalactiae (Arends et al, 2013; Goessweiner-Mohr et al, 2013 a and b; 2014 a and b; Fercher et al, 2016;Grohmann et al, 2016;Kohler et al, 2017;Laverde et al, 2017). The conjugation machines in Gram + species differ from their Gramspecies counterparts mainly by lacking the outer membrane core complex and the VirB11 ATPase.…”

Section: Conjugative Transfer Systemsmentioning

confidence: 99%

Type IV Secretion in Gram-Negative and Gram-Positive Bacteria

2017

Current Topics in Microbiology and Immunology

View full text Add to dashboard Cite

Type IV secretion systems (T4SSs) are versatile multiprotein nanomachines spanning the entire bacterial cell envelope in Gram-negative and Gram-positive bacteria. They play important roles through the contactdependent secretion of effector molecules into eukaryotic hosts and conjugative transfer of mobile DNA elements as well as contact-independent exchange of DNA with the extracellular milieu. In the last few years, many details on the molecular mechanisms of T4SSs have been elucidated. Exciting structures of T4SS complexes from Escherichia coli plasmids R388 and pKM101, Helicobacter pylori and Legionella pneumophila have been solved. The structure of the F-pilus was also reported and surprisingly revealed a filament composed of pilin subunits in 1:1 stoichiometry with phospholipid molecules. Many new T4SSs have been identified and characterized, underscoring the structural and functional diversity of this secretion superfamily. Complex regulatory circuits also have been shown to control T4SS machine production in response to host cell physiological status or a quorum of bacterial recipient cells in the vicinity. Here, we summarize recent advances in our knowledge of 'paradigmatic' and emerging systems, and further explore how new basic insights are aiding in the design of strategies aimed at suppressing T4SS functions in bacterial infections and spread of antimicrobial resistances.

show abstract

Targeting Type IV Secretion System Proteins to Combat Multidrug-Resistant Gram-positive Pathogens

Cited by 13 publications

References 44 publications

Type IV secretion in Gram‐negative and Gram‐positive bacteria

Type IV secretion in Gram‐negative and Gram‐positive bacteria

Biofilm Forming Antibiotic Resistant Gram-Positive Pathogens Isolated From Surfaces on the International Space Station

Type IV Secretion in Gram-Negative and Gram-Positive Bacteria

Contact Info

Product

Resources

About